Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-beta peptide
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Free Radic Biol Med. 2007 Dec 1;43(11):1552-9. Epub 2007 Aug 29
Hayashi T, Shishido N, Nakayama K, Nunomura A, Smith MA, Perry G, Nakamura M.
Hokkaido Institute of Public Health, Kita 19, Nishi 12, Kita-ku, Sapporo 060-0819, Japan
The lipid peroxidation product 4-hydroxy-2-nonenal (HNE) is proposed to be a toxic factor in the pathogenesis of Alzheimer disease. The primary products of lipid peroxidation are phospholipid hydroperoxides, and degraded reactive aldehydes, such as HNE, are considered secondary peroxidation products. In this study, we investigated the role of amyloid-beta peptide (Abeta) in the formation of phospholipid hydroperoxides and HNE by copper ion bound to Abeta. The Abeta(1-42)-Cu(2+) (1:1 molar ratio) complex showed an activity to form phospholipid hydroperoxides from a phospholipid, 1-palmitoyl-2-linoleoyl phosphatidylcholine, through Cu(2+) reduction in the presence of ascorbic acid. The phospholipid hydroperoxides were considered to be a racemic mixture of 9-hydroperoxide and 13-hydroperoxide of the linoleoyl residue. When Cu(2+) was bound to 2 molar equivalents of Abeta(1-42) (2 Abeta(1-42)-Cu(2+)), lipid peroxidation was inhibited. HNE was generated from one of the phospholipid hydroperoxides, 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH), by free Cu(2+) in the presence of ascorbic acid through Cu(2+) reduction and degradation of PLPC-OOH. HNE generation was markedly inhibited by equimolar concentrations of Abeta(1-40) (92%) and Abeta(1-42) (92%). However, Abeta(1-42) binding 2 or 3 molar equivalents of Cu(2+) (Abeta(1-42)-2Cu(2+), Abeta(1-42)-3Cu(2+)) acted as a pro-oxidant to form HNE from PLPC-OOH. These findings suggest that, at moderate concentrations of copper, Abeta acts primarily as an antioxidant to prevent Cu(2+)-catalyzed oxidation of biomolecules, but that, in the presence of excess copper, pro-oxidant complexes of Abeta with Cu(2+) are formed.
PubMed ID and Record
Free Radic Biol Med. 2007 Dec 1;43(11):1552-9. Epub 2007 Aug 29
Hayashi T, Shishido N, Nakayama K, Nunomura A, Smith MA, Perry G, Nakamura M.
Hokkaido Institute of Public Health, Kita 19, Nishi 12, Kita-ku, Sapporo 060-0819, Japan
The lipid peroxidation product 4-hydroxy-2-nonenal (HNE) is proposed to be a toxic factor in the pathogenesis of Alzheimer disease. The primary products of lipid peroxidation are phospholipid hydroperoxides, and degraded reactive aldehydes, such as HNE, are considered secondary peroxidation products. In this study, we investigated the role of amyloid-beta peptide (Abeta) in the formation of phospholipid hydroperoxides and HNE by copper ion bound to Abeta. The Abeta(1-42)-Cu(2+) (1:1 molar ratio) complex showed an activity to form phospholipid hydroperoxides from a phospholipid, 1-palmitoyl-2-linoleoyl phosphatidylcholine, through Cu(2+) reduction in the presence of ascorbic acid. The phospholipid hydroperoxides were considered to be a racemic mixture of 9-hydroperoxide and 13-hydroperoxide of the linoleoyl residue. When Cu(2+) was bound to 2 molar equivalents of Abeta(1-42) (2 Abeta(1-42)-Cu(2+)), lipid peroxidation was inhibited. HNE was generated from one of the phospholipid hydroperoxides, 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH), by free Cu(2+) in the presence of ascorbic acid through Cu(2+) reduction and degradation of PLPC-OOH. HNE generation was markedly inhibited by equimolar concentrations of Abeta(1-40) (92%) and Abeta(1-42) (92%). However, Abeta(1-42) binding 2 or 3 molar equivalents of Cu(2+) (Abeta(1-42)-2Cu(2+), Abeta(1-42)-3Cu(2+)) acted as a pro-oxidant to form HNE from PLPC-OOH. These findings suggest that, at moderate concentrations of copper, Abeta acts primarily as an antioxidant to prevent Cu(2+)-catalyzed oxidation of biomolecules, but that, in the presence of excess copper, pro-oxidant complexes of Abeta with Cu(2+) are formed.
PubMed ID and Record
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